JP7456934B2 - Tissue grafts with prefabricated attachment points - Google Patents

Description

This application claims the benefit of U.S. Provisional Application No. 62/656,735, filed April 12, 2018, the contents of which are incorporated herein by reference.

FIELD OF THE INVENTION This application relates to tissue grafts, and more particularly to tissue grafts having prefabricated attachment points.

Membrane tissue grafts are often used as matrices for tissue repair or regeneration, particularly soft tissue repair or regeneration. Typically, such tissue grafts are glued or sutured onto the damaged tissue. Once implanted, the tissue graft can protect damaged tissue and assist in tissue growth and repair. Tissue grafts can even be incorporated into the repaired tissue and become part of the repaired/regenerated tissue.

Certain membranous tissue grafts are relatively mechanically robust, providing mechanical properties suitable for reinforced soft tissue grafts. Suture materials, particularly needles, suitable for microsurgical applications in nerve repair are not always suitable for fixating mechanically strong tissue-based membranes. For example, a needle with a larger diameter and cutting edge may be required to prevent needle bending in a membranous tissue graft . However , the use of such needles can be disadvantageous since microsurgical work is better performed using thinner tapered point needles, which can cause less tissue trauma during use.

Certain other membrane tissue grafts have relatively weak mechanical properties to facilitate their use as cushioning or lubricating materials. In such cases, the characteristics of the graft may be such that tearing or tearing occurs primarily due to suture placement. Such tears or tears can easily propagate through the material and cause mechanical failure.

Certain membranous tissue grafts may be formed into tubes or conduits, or other forms to support and enhance microsurgical repairs, such as the repair of damaged nerves. Due to the specialized needs of microsurgical repair, suture and suture needle parameters can be important to the surgical procedure. Thus, a membranous tissue graft that can be sutured with any suture type without damaging the graft, suture needle, or underlying tissue and while preserving the bulk mechanical properties of the graft. desired.

The present disclosure provides membranous tissue grafts designed to avoid, reduce, or minimize suturing difficulties. In some embodiments, the membrane tissue graft includes one or more prefabricated attachment points.

One or more of the following features may be included : Membrane tissue grafts can have a thickness of 25 microns to 3 millimeters. Membrane tissue grafts may include natural materials. Natural materials include pig small intestine submucosa, amniotic membrane/chorion, reconstituted denatured collagen, collagen, elastin, thrombin, fibronectin, starch, poly(amino acids), gelatin, alginate, pectin, fibrin, oxidized cellulose, chitin, and chitosan. , tropoelastin, hyaluronic acid, fibrin-based materials, collagen-based materials, hyaluronic acid-based materials, glycoprotein-based materials, cellulosic materials, silk, and combinations thereof . Membrane tissue grafts may include synthetic materials. Synthetic materials include silicone resin, expanded polytetrafluoroethylene (ePTFE), polyethylene terephthalate tetraphthalate (Dacron), polyurethane aliphatic polyester, poly(amino acid), poly(propylene fumarate), copoly(ether ester), polyalkylene From oxalates, polyamides, tyrosine-derived polycarbonates, poly(iminocarbonates), polyorthoesters, polyoxaesters, polyamide esters, polyoxaesters containing amine groups, poly(anhydrides), polyphosphazenes, and mixtures thereof. You can choose . Membrane tissue grafts may include one or more bioactive components that facilitate repair of damaged tissue. The one or more prefabricated attachment points can include one or more prefabricated suture holes. One or more prefabricated attachment points may be placed near the outer edge of the membranous tissue graft. The membranous tissue graft may be in the form of a tube, and one or more prefabricated attachment points may be placed along the edges of the two ends of the tube . The membranous tissue graft may be rectangular, and the one or more prefabricated attachment points may be placed along two opposite sides of the rectangular membranous tissue graft and along the other two opposite sides. It doesn't have to exist. One or more prefabricated attachment points may be placed along the edge of the membranous tissue graft at a distance of about 0.5 mm to about 10 mm from the edge.

The one or more prefabricated attachment points may include one or more markings disposed on the membrane tissue graft and configured to increase visibility of the one or more prefabricated attachment points. The membranous tissue graft is in the shape of a tube, and one or more markings can be placed along the edges of the two ends of the tube. The membranous tissue graft may be rectangular and the one or more markings may be located along two opposite sides of the rectangular membranous tissue graft without being present along the other two opposite sides. good. The one or more markings may be positioned along the edge at a distance from the edge of the tissue graft from about 0.5 mm to about 10 mm . The one or more markings indicate the orientation of the membrane tissue graft. One or more markings may be placed to assist a user in placing tissue at a measured distance within the membranous tissue graft. The one or more prefabricated attachment points can include one or more prefabricated suture holes and one or more markings.

In another embodiment, a method of repairing an injured and/or severed nerve is provided. The method may include implanting a membrane tissue graft that includes one or more prefabricated attachment points to the injured and/or severed nerve. The injured and/or severed nerve may have a gap ranging from about 0 millimeters to about 5 millimeters.

The details of one or more example embodiments are set forth in the accompanying drawings and the description below. Other possible exemplary features and/or possible exemplary advantages will become apparent from the description, the drawings, and the claims. Some embodiments may not have those possible example features and/or possible example advantages; may not necessarily be required in some embodiments.

Examples of one or more prefabricated attachment points (e.g., one or more prefabricated etches and one or more prefabricated suture holes) in exemplary membranous tissue grafts of the present disclosure show. 3 illustrates exemplary shapes and configurations of suture holes. In each embodiment, the fill toward the center indicates a hole or cut. White areas around the holes indicate any etching. Further, a shaded area surrounding the white area indicates an arbitrary reinforced area. One of various configurations of one or more prefabricated attachment points, particularly one or more prefabricated holes or suture holes disposed on the membranous tissue graft, consistent with embodiments of the present disclosure. shows. One of various configurations of one or more prefabricated attachment points, particularly one or more prefabricated holes or suture holes disposed on the membranous tissue graft, consistent with embodiments of the present disclosure. shows. One of various configurations of one or more prefabricated attachment points, particularly one or more prefabricated holes or suture holes disposed on the membranous tissue graft, consistent with embodiments of the present disclosure. shows. One of various configurations of one or more prefabricated attachment points, particularly one or more prefabricated holes or suture holes disposed on the membranous tissue graft, consistent with embodiments of the present disclosure. shows. Illustrated is one of various configurations of one or more prefabricated attachment points, particularly one or more prefabricated etchings or markings disposed on a membranous tissue graft, consistent with embodiments of the present disclosure. . Illustrated is one of various configurations of one or more prefabricated attachment points, particularly one or more prefabricated etchings or markings disposed on a membranous tissue graft, consistent with embodiments of the present disclosure. . 1 illustrates one of various configurations of one or more prefabricated attachment points, specifically one or more prefabricated etchings or markings disposed on a membrane tissue graft, consistent with embodiments of the present disclosure. Illustrated is one of various configurations of one or more prefabricated attachment points, particularly one or more prefabricated etchings or markings disposed on a membranous tissue graft, consistent with embodiments of the present disclosure. . Figure 3 illustrates an example of the presently disclosed membrane tissue graft in a nerve repair protector tissue graft. Figure 3 illustrates an example of a membrane tissue graft of the present disclosure in a nerve repair connector tissue graft.

In certain exemplary embodiments, the present disclosure provides one or more prefabricated attachment points (e.g., prefabricated attachment points to increase visibility and/or to reinforce suture points). A membranous tissue graft can be provided with a suture hole and surrounding features).

In certain exemplary embodiments, the tissue graft of the present disclosure may be in the form of a tube designed to be implanted over injured tissue, such as an injured nerve. In other embodiments, the tissue graft of the present disclosure may be in the form of a sheet designed to be implanted onto the surface of injured tissue, such as an injured nerve.

Suture holes in some embodiments of tissue grafts consistent with the present disclosure may facilitate suturing of the tissue graft to injured tissue, such as an injured nerve. Etching or other methods can be used to increase the visibility of suture holes.

In some exemplary embodiments, the tissue grafts of the present disclosure have no gaps, or have a gap between the severed nerve stumps, such as a severed nerve with a gap of less than about 5 mm. Suitable for repairing damaged nerves. Accordingly, methods of using the tissue grafts of the present disclosure are also described. These methods include, for example, methods of repairing injured or severed nerves by implanting tissue grafts of the present disclosure into the injured or severed nerves. Tissue grafts consistent with this disclosure may be utilized for other purposes.

Tissue grafts are typically glued or sutured to the injured tissue. Membrane tissue grafts and/or injured tissue may be damaged due to problems associated with suturing (e.g., needle bending or blunting due to the relatively mechanically tough tissue-based membrane), which causing more extensive trauma to the neural tissue and may be damaged due to pressure exerted on the graft after suturing, tearing during suturing or tearing, etc.).
In certain embodiments, the present disclosure uses one or more prefabricated attachment points (e.g., suture holes and/or Membrane tissue grafts can be provided with markings (such as etchings) designed to increase visibility.

Referring to the examples of FIGS. 1-12, in some embodiments, a "membrane tissue graft" as used herein generally refers to Refers to suitable relatively thin grafts. Membrane tissue grafts (eg, membrane tissue graft 102) may be made from any of a variety of synthetic and/or natural materials . The membranous tissue graft (e.g., membranous tissue graft 102) can be, for example, about 25 microns to 3 mm, 100 microns to 2.75 mm, 200 microns to 2.5 mm, 300 microns to 2 mm, or 500 microns to 1.5 mm thick. It can have some characteristics. In one embodiment, the thickness is about 100 microns. However, it is understood that the membrane tissue graft can have any thickness within the scope of this disclosure.

In some embodiments, the membranous tissue graft (eg, membranous tissue graft 102) may be constructed from natural materials such as porcine small intestinal submucosa, amniotic membrane/chorion, or reconstituted denatured collagen. Also, membrane tissue grafts (eg, membrane tissue graft 102) may be made from synthetic materials. In preferred embodiments, the membranous tissue graft (eg, membranous tissue graft 102) may be non-immune to the recipient.

Synthetic materials suitable for use in membrane tissue grafts include silicone membranes, expanded polyethylene terephthalate (ePTFE), polyethylene tetrafuslate (Dacron), polyurethane aliphatic polyesters, poly(amino acids), poly(propylene fumarate). , copoly(ether esters), polyalkylene oxalates, polyamides, tyrosine-derived polycarbonates, poly(iminocarbonates), polyorthoesters, polyoxaesters, polyamide esters, polyoxaesters containing amine groups, poly(anhydrides) , polyphosphazenes, and mixtures thereof.

Natural polymers suitable for use in membrane tissue grafts include collagen, elastin, thrombin, fibronectin, starch, poly(amino acids), gelatin, alginate, pectin, fibrin, oxidized cellulose, chitin, chitosan, tropoelastin, These include, but are not limited to, hyaluronic acid, fibrin-based materials, collagen-based materials, hyaluronic acid-based materials, glycoprotein-based materials, cellulosic materials, silk, and combinations thereof.

Combinations of one or more natural and/or synthetic materials may also be used. In particular, any combination of natural and/or synthetic materials disclosed in the previous paragraph can be used.

As used herein, "nerve graft" generally refers to a graft that is transplanted into a recipient to repair damaged nerves or other tissues of the nervous system. Neural grafts can be made from synthetic materials, natural materials, or combinations thereof. The various materials used to prepare membranous tissue grafts described above may also be used in preparing nerve grafts.

In an exemplary embodiment, the membranous tissue graft may include porcine submucosa extracellular matrix ("ECM"). In certain exemplary embodiments, a tissue graft can include ECM in the form of a sheet that can be wrapped around injured tissue, such as an injured nerve. An example of such a membrane tissue graft is the modified AxoGuard Nerve Protector®, described in Example 1 below.

In a further embodiment the membranous tissue graft is suitable for joining a severed nerve with a short gap or no gap, preferably with a gap of less than 5 mm between the severed stumps. It may contain ECM in the form of a tube. An example of such a membrane tissue graft is the modified AxoGuard Nerve Connector®, described in Example 2 below.

In another example, a membranous tissue graft can include, for example, minimally processed human umbilical cord membrane that can be used as a resorbable soft tissue overlying separate tissue layers. An example of such a tissue graft is Avive Soft Tissue® modified according to embodiments of the present invention.

In some embodiments, membranous tissue grafts (eg, membranous tissue graft 102) may be used with tendon wraps and repairs. For example, membrane tissue embodiments can wrap to strengthen the repair, can aid in anti-adhesion, and/or can aid in detensioning . Membrane tissue grafts also include other types of tissue, including blood vessels, intestines, muscles (e.g., cardiac, skeletal, and smooth muscle), neural tissue (e.g., nerves, brain, and spinal cord), connective tissue, epithelial tissue, etc. can be used with other tissues.

In certain embodiments, the membranous tissue grafts of the present disclosure may include one or more bioactive components that facilitate repair of damaged nerves. Non-limiting examples of such bioactive compounds include foreign or autologous growth factors, proteins (including matrix proteins), peptides, antibodies, enzymes, platelets, glycoproteins, hormones, cytokines, glycosaminoglycans, These include nucleic acids, analgesics, viruses, viral particles, cells, non-steroidal anti-inflammatory drugs, cells and cell components, or immunosuppressive therapies . In certain embodiments, bioactive ingredients suitable for use in the membrane tissue grafts of the present disclosure include interleukins, tissue inhibitors of metalloproteinases, epidermal growth factors, fibroblast growth factors, platelet-derived growth factors, vascular endothelium. including growth factors, and transforming growth factors. In a preferred embodiment, the bioactive growth factor is brain-derived neurotrophic factor (BDNF), glial cell-derived neurotrophic factor (GDNF), neurotrophic factor (NGF), neutrophil-3 (NT-3), ciliary body including neurotrophic growth factors such as neurotrophic factor (CNTF) or leukemia inhibitory factor (LIF).

As used herein, "prefabricated" generally refers to forming components or features prior to use of the membrane tissue graft in connection with tissue repair. For example, in some embodiments one or more prefabricated attachment points (e.g., one or more prefabricated attachment points 104) may be formed or created during manufacture of the membrane tissue graft. . In this manner, prior to using the membrane tissue graft 102 in connection with tissue repair, one or more prefabricated attachment points 104 (e.g., prefabricated holes 106 and/or one or more A prefabricated etch 108) can be formed or defined . In some embodiments, the membrane tissue graft 102 may be manufactured without one or more prefabricated attachment points 104 (e.g., prefabricated holes 106 and/or prefabricated etches 108). However, one or more prefabricated attachment points 104 (e.g., prefabricated holes 106 and/or one or more prefabricated etching 108) . In this manner, the membranous tissue graft 102 has one or more prefabricated attachment points 104 (e.g., prefabricated holes 106 and/or or one or more pre-fabricated etches 108).

A "suture hole" or "hole" as used herein generally refers to a preformed hole or cut in a membranous tissue graft. For example, a surgeon can use pre-formed suture holes (eg, pre-formed holes 106) to suture the tissue graft to the target site. Pre-formed suture holes (e.g., pre-formed holes 106) can avoid the need to drill the membranous tissue graft during surgery and, therefore, avoid suturing with the potential for subsequent tissue damage. The possibility of damaging the thread needle can be reduced, allowing any suture/needle combination to be used with equal ease . Also , with reference to the example of FIG. 2 and some embodiments, a suture hole (e.g., prefabricated hole 106) may be replaced by a "+" symbol (e.g., prefabricated hole 202), a "-" ” symbol (e.g., prefabricated hole 204), "x" symbol (e.g., prefabricated hole 206), triangle (e.g., prefabricated hole 208), circle (e.g., prefabricated hole 210). ), square, rectangular, semicircular, wavy, "serrated, ratcheted" designs, etc., can be any of a variety of shapes or combinations of shapes.

In some embodiments, suture holes may be present near the outer edge of the membranous tissue graft. In some embodiments, suture holes can be present around the entire circumference of the membranous tissue graft. Also, with reference to the example of FIG. 3 and some embodiments, suture holes (e.g., pre-fabricated holes 306) may, for example, May be present along the outer edge . For example , if the tissue graft is rectangular, suture holes may be present along two opposite sides of the rectangle and not along the other two opposite sides of the rectangle. Similarly, if the tissue graft is circular, suture holes may be present along a portion of the circumference opposite the center.

Referring again to the example of FIG. 3, in some embodiments the membranous tissue graft (e.g., membranous tissue graft 302) may be in the form of a tube, with suture holes (e.g., pre-fabricated holes 306). ) may be present along the edges of the two ends of the tube. Such a graft may be used in nerve repair to connect injured or severed nerves, and the two edges of the tube may be sutured to the two stumps of the injured or severed nerve . Although an example of using this example graft for nerve repair has been provided, it is understood that the membrane tissue graft can be for any type of tissue repair. For example, in some embodiments, membrane tissue grafts can be used with tendon repair.

Also, referring to the example of FIG. 4 and some embodiments, the membranous tissue graft (e.g., membranous tissue graft 402) can be rectangular in shape, with suture holes (e.g., pre-fabricated holes 406) may exist along two opposite sides of the rectangle. Such membranous grafts are designed to attach to the severed nerve or injury in such a way that rectangular sides with suture holes surround the severed part of the nerve and these sides are sutured to the two stumps of the severed nerve. It can be used in nerve repair by wrapping damaged nerves . Although an example is provided of wrapping a rectangular membranous tissue graft around a nerve , it is understood that the membranous tissue graft can be wrapped around any tissue. For example, in some embodiments, a rectangular membrane tissue graft can be wrapped around a tendon . Also , referring to the example of FIG. 5 and some embodiments, suture holes (e.g., pre-fabricated holes 506) extend around the entire circumference of a rectangular membranous tissue graft (e.g., membranous tissue graft 502). It can exist . Also , referring to the example of FIG. 6 and some embodiments, suture holes (e.g., pre-fabricated holes 606) are present throughout a rectangular membranous tissue graft (e.g., membranous tissue graft 602). It is possible. Although FIG. 6 shows rows and columns of suture holes, it is understood that the suture holes (eg, prefabricated holes 606) may be arranged in any pattern or configuration within the scope of this disclosure.

In some embodiments, the suture hole is located at the edge of the membranous tissue graft at a distance of about 0.5 mm to about 10 mm, such as about 1 mm to about 3 mm, and in some embodiments about 1 mm. may exist along the section. However, it is understood that the suture hole may be located any distance from the end of the membrane tissue graft within the scope of the present disclosure.

Referring again to the example of FIG. 1, in some embodiments, "etching" as used herein generally means that a portion of the material forming the membranous tissue graft is removed and separated from the surrounding material. Refers to a site or location within a membranous tissue graft that has a different surface roughness, thus creating an area that is visually distinct from the rest of the membranous tissue graft . In some embodiments, the site of etching (eg, one or more prefabricated etches 108) may not include holes through the membrane tissue graft. For example, in some embodiments, the surgeon may use the Preformed etches (eg, one or more prefabricated etches 108) may be used. Additionally, the etchings (eg, one or more prefabricated etchings 108) can be used as guidance marks to indicate other surgically relevant information, such as the distance between nerve endings within the nerve conduit . Accordingly , the terms "etching" and "marking" may be used interchangeably within the scope of this disclosure. In some embodiments, the etches (eg, one or more prefabricated etches 108) can be any of a variety of shapes or combinations of shapes, such as squares, triangles, semicircles, etc.

In certain embodiments, the etching or marking may be present or located near the outer edge of the tissue graft. However, it is understood that the etching may be located around the entire circumference of the tissue graft. Alternatively, the etching may be located or located only along the perimeter of opposite sides of the tissue graft . For example , if the tissue graft is rectangular, the etching may be located or present along two opposite sides of the rectangle and not present along the other two opposite sides of the rectangle. Similarly, if the tissue graft is circular or elliptical, the etching may be present along a portion of the circumference opposite the center.

Also, referring to the example of FIG. 7 and some embodiments, a membranous tissue graft (e.g., membranous tissue graft 702) may be in the form of a tube and may be etched (e.g., one or more prefabricated etchings 708) may be present or located along the edges of the two ends of the tube. Such membranous grafts can be used in nerve repair to connect injured or severed nerves, and the two edges of the tube can be sutured to the two stumps of the injured or severed nerve. .

Also, referring to the example of FIG. 8 and some embodiments, a membrane tissue graft (e.g., membrane tissue graft 802) may be rectangular and may include an etching (e.g., one or more prefabricated etchings). 808) may exist along two opposite sides of the rectangle, and may not exist along the other two opposite sides . Such a graft can be used for nerve repair by wrapping a severed or damaged nerve, so that the rectangular sides with the etchings surround the nerve and these sides overlap the severed nerve. The two stumps can be sutured. Although an example of wrapping a membranous tissue graft around a nerve is provided, it is understood that the membranous tissue graft can be wrapped around any tissue. For example, in some embodiments, a membrane tissue graft can be wrapped around a tendon . Also , referring to the example of FIG. 9 and some embodiments, an etch (e.g., prefabricated etch 908) is present around the entire circumference of a rectangular membranous tissue graft (e.g., membranous tissue graft 902). obtain . Also , referring to the example of FIG. 10 and some embodiments, an etch (e.g., prefabricated etch 1008) may be present throughout a rectangular membranous tissue graft (e.g., membranous tissue graft 1002). . Although FIG. 10 shows rows and columns of etches, it is understood that the etches (eg, prefabricated etching 1008) may be arranged in any pattern or configuration within the scope of this disclosure.

In some embodiments, the etching is at a distance of about 0.2 mm to about 1.5 mm, in some embodiments about 0.5 mm to about 1.25 mm, and in some embodiments about 1 mm. , may be present as a ring along the edge of the membranous tissue graft . The etching may be preformed in conjunction with a preformed hole in which the etched ring has a width of between 50 microns and 1 millimeter, preferably about 100 microns.

Also, referring to the example of FIG. 11 and some embodiments, an etched mark (e.g., prefabricated etching 1108) is present in a central portion of a membranous tissue implant (e.g., membranous tissue implant 1102). and can help position and guide the placement of the membranous tissue graft . One embodiment of the etched mark includes a "dash" of about 200 microns by 1 millimeter, which can assist the surgeon in placing tissue at measured distances within the membranous tissue graft. For example, one or more etches may be used to allow a surgeon to place a nerve end within a membranous tissue graft at a measured distance within the membranous tissue graft (e.g., a measured distance within membranous tissue graft 1102). to assist . In some embodiments, one or more markings may facilitate placement of multiple tissue edges at a measured distance from each other. For example, one or more markings or etchings may be used by a surgeon to determine when tissue or nerve endings are within a membranous tissue graft, for example, within 1 millimeter of each other (e.g., within a membranous tissue graft 1102, at a measured distance from each other). and the placement of tissue at each end) . However , one or more markings are arranged to assist the surgeon in determining when multiple tissue edges are within any measured distance from each other and/or from the ends of the membranous tissue graft. It is understood that this may be done.

In some embodiments, a membranous tissue graft may include one or more prefabricated attachment points (e.g., one or more prefabricated attachment points 104) that include one or more prefabricated attachment points 104. It may include at least one of a prefabricated hole (e.g., one or more prefabricated holes 106) and one or more etches (e.g., one or more prefabricated etches 108) . For example , referring again to the example of FIG. 11, a membrane tissue graft 1102 (e.g., a nerve repair protector tissue graft) has one or more prefabricated holes 1106 and one or more prefabricated etches 1108. can include. In this way, when a surgeon uses one or more pre-fabricated holes 1106 to repair tissue using membrane tissue graft 1102, one or more pre-fabricated etches 1108 can be Guided by direction . In this example, a predefined spacing between prefabricated attachment points of 2 millimeters is shown. However, it is understood that any spacing between prefabricated attachment points (e.g., prefabricated holes 1106 and/or prefabricated etches 1108) can be used within the scope of this disclosure. .

Also, with reference to the example of FIG. 12 and some embodiments, the membrane tissue graft 1202 (e.g., nerve repair connector tissue graft) includes one or more pre-made holes 1206.

Referring again to the example of FIG. 2, in some embodiments, etchings (e.g., etchings 212, 214, 216, 218, 220) are combined with suture holes (e.g., prefabricated holes 202, 204, 206, 208). , 210), the visibility of the hole can be increased, for example with a ring of etched areas surrounding the hole . In such embodiments, the improved visibility of the hole represented by the etching allows the surgeon to suture the membranous tissue graft by suturing through the hole. Alternatively, reinforcing regions including thickened regions of material (e.g., reinforcing regions 222, 224, 226, 228, 230) forming tissue grafts or substitute materials are used to provide visual contrast in a similar manner. be able to . The reinforcing regions (eg, reinforcing regions 222, 224, 226, 228, 230) can also include a support material, such as an adhesive or a ring of support fibers or wire surrounding the hole. The reinforcement area can be any shape surrounding the hole, such as circular, oval, oval, square, triangular, rectangular.

In some embodiments, the etching and/or suture hole can include additional markings that further enhance the visibility of the etching and/or suture hole. The markings can be placed and designed to indicate the orientation of the membranous tissue graft. For example, markings in certain asymmetric regions of a rectangular membranous tissue graft can be used to indicate two surfaces of the membranous tissue graft due to asymmetric positioning of the markings.

In some embodiments, the etched and/or suture holes in the membranous tissue graft of the present disclosure can facilitate suturing of the membranous tissue graft to injured tissue, such as an injured nerve. Accordingly, methods of using the membranous tissue grafts of the present disclosure, such as methods of repairing damaged tissue (eg, a damaged or severed nerve or a damaged tendon), are also described.

In some exemplary embodiments, the present disclosure may provide methods for repairing damaged nerves, particularly damaged or severed nerves that do not have a gap or have a gap, e.g., less than about 5 mm, between the severed nerve stumps. In these methods, a membrane tissue graft in the form of a tube may be sutured to the severed ends of the damaged nerve . The implantation of such a tissue graft may allow the body's natural healing process to repair the severed nerve by isolating and protecting the severed nerve during the healing process. For example, the patient's cells may be incorporated into the extracellular matrix to reconstruct and form tissue similar to the neuroepithelium.

In certain other cases of nerve injury where the injured nerve has no gap or a small gap, e.g. less than about 5 mm, a membranous tissue graft in the form of a rectangle is wrapped around the injured nerve. , such a membrane is sutured to the injured nerve.

Implantation of the membranous tissue graft of the present disclosure has the potential to protect injured nerves and augment nerve reconstruction. The suture hole may facilitate the use of any suture, especially when a suture needle is not mechanically suitable for the membranous tissue graft. Membrane tissue grafts are designed to protect and isolate and may separate and protect the injured nerve from surrounding tissue during the healing process. The patient's cells are incorporated into a minimally processed extracellular matrix to remodel and form a tissue similar to the epineurium.

(definition)
As used herein, the singular form (a) is intended to include the plural form as well, unless the context clearly dictates otherwise. Additionally, to the extent that the terms "comprising,""having,""comprising," or variations thereof are used in either the detailed description and/or the claims, these terms are interchangeable with the term "comprising." is intended to be comprehensive in manner . " Comprising,""consisting essentially of," and "consisting of" can be used interchangeably.

The phrase "consisting essentially of" includes embodiments in which the claims include the specified materials or steps, and embodiments that do not substantially affect the essential novel features of the claims. Show that.

The term "about" means within an acceptable error range for a particular value as determined by one of ordinary skill in the art, which is dependent in part on how the value is measured or determined, i.e., the limitations of the measurement method. Dependent. In the context of the size of various parameters of the membranous tissue grafts of the present disclosure where the term "about" is used, these parameters are defined as having a variation of 0 to 10% (X±10%) around the stated value ( within the error range).

In this disclosure, ranges are written in a concise manner to avoid having to establish a length and describe each and every value within the range. Any suitable value within the range may be selected as the upper, lower, or end value of the range, where appropriate. For example, a range of 0.1 to 1.0 includes end values of 0.1 and 1.0, and 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0 Intermediate values of .8, 0.9, and all values included within 0.1 to 1.0, such as 0.2 to 0.5, 0.2 to 0.8, 0.7 to 1.0, etc. Represents the middle range . Values with at least two significant digits within the range are assumed; for example, a range of 5 to 10 includes everything between 5.0 and 10.0, as well as everything between 5.00 and 10.00, inclusive. indicates the value of

When ranges are used herein, combinations and subcombinations of ranges (e.g., subranges within the disclosed range), specific embodiments therein are intended to be expressly included. Ru.

All patents, patent applications, provisional applications, and publications mentioned or cited herein are hereby incorporated by reference in their entirety, including drawings and tables, to the extent they do not contradict the express disclosure herein. Incorporated.

The following are examples that illustrate procedures for implementing embodiments of the present disclosure. These examples should not be considered limiting.

Example 1: AxoGuard Nerve Connector® (AxoGen, Inc.) Improved According to Embodiments of the Invention
Referring again to the example of FIG. 12, in some embodiments, the AxoGuard Nerve Connector® is used in minimally processed porcine cells for connection-assisted splicing of severed or injured nerves. An outer matrix can be provided. Some aspects of the AxoGuard Nerve Connector® are described in the brochure entitled "Nerve Repair Solution", AxoGen Inc (2015). This brochure is incorporated herein in its entirety.

In this example, the AxoGuard Nerve Connector® may be modified according to embodiments of the invention by providing one or more attachment points (eg, etched and/or suture holes). Such improved AxoGuard Nerve Connector(R) may be used to connect a severed nerve, such as a severed nerve, that has no gap or a gap between the severed nerve stumps, such as a gap of less than about 5 mm. May be suitable for treatment of severed nerves . The improved AxoGuard Nerve Connector® may be in the form of a tube designed to be implanted into an injured nerve. The improved AxoGuard Nerve Connector® is available in 1.5mm x 10mm, 2mm x 10mm, 3mm x 10mm, 4mm x 10mm, 5mm x 10mm, 6mm x 10mm, 7mm x 10mm, 1.5mm x 15mm, 2mm x It can have dimensions of 15 mm, 3 mm x 15 mm, 4 mm x 15 mm, 5 mm x 15 mm, 6 mm x 15 mm, or 7 mm x 15 mm . However , it is understood that the improved AxoGuard Nerve Connector® can have any dimensions within the scope of the present invention.

In some embodiments, the modified AxoGuard Nerve Connector® can have etched and/or suture holes along the edges of the two ends of the tube.

Example 2: AxoGuard Nerve Protector® (AxoGen, Inc.) Improved According to Embodiments of the Invention
AxoGuard Nerve Protector® provides a minimally processed porcine extracellular matrix for wrapping or protecting severed or injured nerves. Specific aspects of AxoGuard Nerve Protector® are described in the catalog "Nerve Repair Solution, AxoGen Inc (2015)". This brochure is incorporated herein in its entirety.

Referring again to the example of FIG. 11, in this example, the AxoGuard Nerve Protector® is modified in accordance with embodiments of the present invention by providing one or more attachment points (e.g., etched and/or suture holes). may be done. Such an improved AxoGuard Nerve Protector® is suitable for cutting nerves that have no gap or a gap between the severed nerve stumps, such as a gap of less than about 5 mm. may be suitable for wrapping and protecting damaged nerves . The improved AxoGuard Nerve Protector® is available in 2mm x 20mm, 3.5mm x 20mm, 5mm x 20mm, 7mm x 20mm, 10mm x 20mm, 3.5mm x 40mm, 5mm x 40mm, 7mm x 40mm, or A tube with a size of 10 mm x 40 mm can be of rectangular shape when wrapped around a damaged or severed nerve . However , it is understood that the improved AxoGuard Nerve Protector® can have any dimensions within the scope of this disclosure.

The improved AxoGuard Nerve Connector® can have etched or suture holes along two sides that encircle the nerve and form the two ends of the tube when the improved AxoGuard Nerve Connector® is wrapped around the severed nerve or other tissue.

The examples and embodiments described herein are for illustrative purposes only, and various modifications or changes in light thereof may suggest to those skilled in the art that they may be considered to be within the spirit and scope of this application and the appended claims. should be understood as falling within the scope of Additionally , any feature or limitation of any invention or embodiment thereof disclosed herein may be considered in conjunction with any and/or all other elements or limitations disclosed herein (individually or (in any combination) or with any other invention or embodiment; all such combinations are contemplated within the scope of this invention, without limitation thereto.
(Additional note)
The technical ideas that can be understood from the above embodiment and modification examples will be described.
[Item 1]
with one or more prefabricated attachment points
Membrane tissue grafts.
[Item 2]
The membranous tissue graft according to item 1,
having a thickness of 25 microns to 3 millimeters
Membrane tissue grafts.
[Item 3]
The membranous tissue graft according to item 1,
Contains natural ingredients
Membrane tissue grafts.
[Item 4]
The membranous tissue graft according to item 3,
The natural materials include pig small intestine submucosa, amniotic membrane/chorion, reconstituted denatured collagen, collagen, elastin, thrombin, fibronectin, starch, poly(amino acids), gelatin, alginate, pectin, fibrin, oxidized cellulose, chitin, selected from chitosan, tropoelastin, hyaluronic acid, fibrin-based materials, collagen-based materials, hyaluronic acid-based materials, glycoprotein-based materials, cellulosic materials, silk, and combinations thereof
Membrane tissue grafts.
[Item 5]
The membranous tissue graft according to item 1,
Contains synthetic materials
Membrane tissue grafts.
[Item 6]
The membranous tissue graft according to item 5,
The synthetic materials include silicone resin, expanded polytetrafluoroethylene (ePTFE), polyethylene terephthalate tetraphthalate (Dacron), polyurethane aliphatic polyester, poly(amino acid), poly(propylene fumarate), copoly(ether ester), poly Alkylene oxalates, polyamides, tyrosine-derived polycarbonates, poly(iminocarbonates), polyorthoesters, polyoxaesters, polyamide esters, polyoxaesters containing amine groups, poly(anhydrides), polyphosphazenes, and mixtures thereof selected from
Membrane tissue grafts.
[Item 7]
The membranous tissue graft according to item 1,
Contains one or more bioactive components that facilitate repair of damaged tissue
Membrane tissue grafts.
[Item 8]
The membranous tissue graft according to item 1,
the one or more prefabricated attachment points include one or more prefabricated suture holes
Membrane tissue grafts.
[Item 9]
The membranous tissue graft according to item 1,
the one or more prefabricated attachment points are positioned near an outer edge of the membrane tissue graft.
Membrane tissue grafts.
[Item 10]
The membranous tissue graft according to item 1,
The membranous tissue graft is in the shape of a tube, and the one or more prefabricated attachment points are positioned along edges of two ends of the tube.
Membrane tissue grafts.
[Item 11]
The membranous tissue graft according to item 1,
the membranous tissue graft is rectangular;
the one or more prefabricated attachment points are located along two opposite sides of the rectangular membranous tissue graft and are absent along two other opposite sides;
Membrane tissue grafts.
[Item 12]
The membranous tissue graft according to item 1,
The one or more prefabricated attachment points are positioned along an edge of the membranous tissue graft at a distance of 0.5 mm to 10 mm from the edge.
Membrane tissue grafts.
[Item 13]
The membranous tissue graft according to item 1,
The one or more prefabricated attachment points include one or more markings disposed on the membranous tissue graft and configured to increase visibility of the one or more prefabricated attachment points.
Membrane tissue grafts.
[Item 14]
The membranous tissue graft according to item 13,
The membranous tissue graft is in the shape of a tube, and the one or more markings are disposed along edges of two ends of the tube.
Membrane tissue grafts.
[Item 15]
The membranous tissue graft according to item 13,
the membranous tissue graft is rectangular;
The one or more markings are located along two opposite sides of the rectangular membranous tissue graft and are absent along two other opposite sides.
Membrane tissue grafts.
[Item 16]
The membranous tissue graft according to item 13,
The one or more markings are positioned along the edge of the tissue graft at a distance from the edge of 0.5 mm to 10 mm.
Membrane tissue grafts.
[Item 17]
The membranous tissue graft according to item 13,
The one or more markings indicate the orientation of the membranous tissue graft.
Membrane tissue grafts.
[Item 18]
The membranous tissue graft according to item 13,
The one or more markings are arranged to assist a user in positioning tissue at a measured distance within the membranous tissue graft.
Membrane tissue grafts.
[Item 19]
The membranous tissue graft according to item 18,
The one or more markings facilitate positioning of multiple tissue edges at a measured distance from each other.
Membrane tissue grafts.
[Item 20]
The membranous tissue graft according to item 1,
The one or more prefabricated attachment points include one or more prefabricated suture holes and one or more markings.
Membrane tissue grafts.
[Item 21]
A method of repairing a damaged and/or severed nerve, the method comprising:
A method comprising implanting a membranous tissue graft containing one or more prefabricated attachment points to the injured and/or severed nerve.
[Item 22]
The method described in item 21,
The injured and/or severed nerve has a gap ranging from 0 mm to 5 mm.
Method.

Claims (21)

A membranous tissue graft comprising one or more prefabricated attachment points, the graft comprising:
the one or more prefabricated attachment points include one or more etchings;
The one or more etchings include:
increasing the visibility of the one or more prefabricated attachment points;
guiding placement of the membranous tissue graft in recipient tissue;
determining the orientation of the membranous tissue graft;
assisting in positioning one or more nerve ends at a measured distance within said membranous tissue graft; and/or
Facilitates placement of multiple nerve ends at measured distances from each other within the membranous tissue graft
is configured for use with
Membrane tissue grafts. The membranous tissue graft according to claim 1,
Membrane tissue grafts having a thickness of 25 microns to 3 millimeters. 2. The membrane tissue graft of claim 1,
Membrane tissue grafts, including natural materials. The membranous tissue graft according to claim 3,
The natural materials include pig small intestine submucosa, amniotic membrane/chorion, reconstituted denatured collagen, collagen, elastin, thrombin, fibronectin, starch, poly(amino acids), gelatin, alginate, pectin, fibrin, oxidized cellulose, chitin, Membrane tissue grafts selected from chitosan, tropoelastin, hyaluronic acid, fibrin-based materials, collagen-based materials, hyaluronic acid-based materials, glycoprotein-based materials, cellulose-based materials, silk, and combinations thereof. The membranous tissue graft according to claim 1,
Membrane tissue grafts containing synthetic materials. The membranous tissue graft according to claim 5,
The synthetic materials include silicone resin, expanded polytetrafluoroethylene (ePTFE), polyethylene terephthalate tetraphthalate (Dacron), polyurethane aliphatic polyester, poly(amino acid), poly(propylene fumarate), copoly(ether ester), poly Alkylene oxalates, polyamides, tyrosine-derived polycarbonates, poly(iminocarbonates), polyorthoesters, polyoxaesters, polyamide esters, polyoxaesters containing amine groups, poly(anhydrides), polyphosphazenes, and mixtures thereof selected from membranous tissue grafts. The membranous tissue graft according to claim 1,
Membrane tissue grafts containing one or more bioactive components to facilitate repair of damaged tissue. The membranous tissue graft according to claim 1,
The one or more prefabricated attachment points include one or more prefabricated suture holes or cuts . The membranous tissue graft. The membranous tissue graft according to claim 1,
The one or more prefabricated attachment points are positioned near an outer edge of the membranous tissue graft. The membranous tissue graft according to claim 1,
The membranous tissue graft is in the shape of a tube, and the one or more prefabricated attachment points are disposed along the edges of two ends of the tube. 2. The membrane tissue graft of claim 1,
the membrane tissue graft is rectangular;
The one or more prefabricated attachment points are disposed along two opposing sides of the rectangular membrane tissue graft and are absent along the other two opposing sides. The membranous tissue graft according to claim 1,
The one or more prefabricated attachment points are positioned along an edge of the membranous tissue graft at a distance of 0.5 mm to 10 mm from the edge. The membranous tissue graft. The membranous tissue graft according to claim 8 ,
The membrane tissue graft is in the shape of a tube, and the one or more etchings are disposed along edges of two ends of the tube. The membranous tissue graft according to claim 8 ,
the membranous tissue graft is rectangular;
The one or more etchings are disposed along two opposite sides of the rectangular membranous tissue graft and are absent along two other opposite sides of the rectangular membranous tissue graft. The membranous tissue graft according to claim 8 ,
The one or more etchings are positioned along the edge of the tissue graft at a distance from the edge of 0.5 mm to 10 mm. Membrane tissue graft according to any one of claims 1 to 15 for use in the repair of injured and/or severed nerves, comprising:
grafted onto said injured and/or severed nerve;
Membrane tissue grafts . 17. The membranous tissue graft according to claim 16 ,
The injured and/or severed nerve has a gap in the range of 0 mm to 5 mm.
Membrane tissue grafts . 9. The membrane tissue graft of claim 8,
The one or more etchings are each formed around the one or more suture holes or cuts.
Membrane tissue grafts. The membranous tissue graft according to claim 1,
the membranous tissue graft is in the form of a tube or sheet;
the one or more prefabricated attachment points include one or more prefabricated suture holes or cuts;
the one or more etchings or the one or more suture holes or cuts are located in one or both of an outer edge portion and a central portion of the tube or the sheet;
Membrane tissue grafts. The membranous tissue graft according to claim 1,
the membrane tissue graft includes two or more etchings;
At least one etching of the two or more etches differs from another etching of the two or more etchings in at least one of shape and size. A membranous tissue graft. The membranous tissue graft according to claim 1,
The implant includes one or more etchings on the outside of the implant.
Membrane tissue grafts.

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